HEPATOMA

Dr Isbandiyah, SpPD

 Hepatocellular carcinoma (HCC) is a

primary malignancy of the liver.
It is now the third leading cause of
cancer deaths worldwide, with over
500,000 people affected.
More common in men than women
(4:1)
Hepatitis (Hepatitis B or hepatitis C)
and excessive alcohol are the leading
causes of HCC.

Malignant Transformation
Multistep
HCC[2]
Epigenetic
alterations
Genetic
Dysplastic nodules[1]
alterations
Liver cirrhosis
Hepatitis C
Hepatitis B
Ethanol
NASH
Normal liver

Risk Factor
HBV

 Microscopically, there are four cytological

types:
fibrolamellar,
pseudoglandular (adenoid),
pleomorphic (giant cell) and
clear cell.

HCC may present with

right upper quadrant pain,
weight loss,
jaundice,
bloating from ascites,
and signs of decompensated liver
disease.

Diagnostic Procedures
In patients with lesions less than 1
cm, >>>> conservative
management with close follow-up
and no biopsy is recommended.
In patients with 1- to 2-cmlesions,
abiopsy should be performed,.
Patients with lesions greater than 2
cm, cirrhosis, characteristic imaging
studies, and elevated AFP values can
be managed without biopsy.
Patients with large tumors who are
not candidates for resection or
transplantation, >>>>>> biopsy is
frequently not indicated.

AJCC/UICC Classification
System

Child-Pugh score
The Child-Pugh score is used to
assess the prognosis of chronic liver
disease, mainly cirrhosis. To
determine treatment required and
the necessity of liver
transplantation.
The score employs five clinical measures
of liver disease. Each measure is scored
1-3, with 3 indicating most severe
derangement.

Chronic liver disease is classified into

Child-Pugh class A to C, employing
the added score from above.

Management of Hepatocellular
Carcinoma Requires a Multidisciplinary
Approach
Hepatobilia
ry Surgery
Hepatolo
gy

Oncolog
y

Pathology

Radiolog
y
Radiation
Oncology

Treatment/Management

Surgical resection
Liver transplantation
Percutaneous ablation
Alcohol injection
Radiofrequency ablation

Radical

Potentially
Curative

Transarterial embolization and

chemoembolization
Chemotherapy.

Palliative

Staging Strategy and Treatment for

Patients With HCC
HCC
PST 0, Child-Pugh A

PST 0-2, Child-Pugh A-B

PST > 2, Child-Pugh C

Very early stage Early stage Intermediate stage Advanced stage

Single < 2 cmSingle or 3 nodules Multinodular, PST 0 Portal invasion,
3 cm, PST 0
N1, M1, PST 12
Single

3 nodules 3 cm

Portal pressure/bilirubin
Increased
Normal
Resection

Terminal
stage

Portal invasion,
N1, M1

Associated
diseases

No
Liver transplant

Yes
PEI/RF

Curative treatments

Llovet JM, et al. J Natl Cancer Inst.

2008;100:698-711.

No
TACE

Yes

Sorafenib
Symptomatic
(unless LT)

 Important features that guide

treatment include:

Size
Spread (stage)
Involvement of liver vessels
Presence of a tumor capsule
Presence of extrahepatic
metastases
Vascularity of the tumor

Surgery: Resection and Transplantation

Surgery is the mainstay of HCC treatment and

achieve the best outcomes in well-selected
candidates.
Less than 5% patients resectable
Factors affecting resectability:
Size<5cm
number of tumors
involvement of major structures
hepatic function
no extra-hepatic spread
no portal hypertension
Requires experienced surgical and supporting team

5 year survival 60%-70%

3 year recurrence 45 - 60%

Transplantation

Milan Criteria :
Single HCC 5 cm or
Up to three nodules 3 cm
No extra hepatic spread
About 10 % qualify for listing
The major drawback of
transplantation is
The scarcity of donors.
The long waiting time.

Percutaneous Treatments

For patients who cannot undergo

resection.
Complete responses in more than 80% of
tumors smaller than 3 cm in diameter, but
in 50% of tumors of 3-5 cm in size.
5-year survival rates of 40%-60%.
reported in patients with small single
tumors, commonly <2 cm in diameter.
Although these treatments provide good
results, they are unable to achieve
response rates and outcomes comparable
with surgical treatments.
Transarterial Embolization and
Chemoembolization is recommended as
first line non-curative therapy for nonsurgical patients with large/multifocal
HCC who do not have vascular invasion or

Percutaneous Ethanol Injection

207 patients with cirrhosis +

HCC < 5 cm
100% Ethanol
Follow up was 25 months
No complications
4.3 sessions per patient
88% complete necrosis
1 ,2,3-year survival rates:
90,80,63%
Cancer 1992;69:925

Radiofrequency Ablation

Palliative Therapies
Primary treatment for unresectable HCC.
Embolization agents usually gelatin or
microspheres may be administered
together with selective intra-arterial
chemotherapy mixed with lipiodol
(chemoembolization).
Doxorubicin, mitomycin and cisplatin are
the commonly used antitumoral drugs.
Arterial embolization achieves partial
responses in 15-55% of patients, and
significantly delays tumour progression
and vascular invasion.

Transarterial Chemoembolization

Meta-analysis of 7 randomized
controlled trials

2 yr survival: 41% (19-63%)

Treatment response: 35% (16-61%)
Risks:

Infection
Tumor lysis syndrome
Hepatic failure

Llovel J He aloI2003"37:429

Systemic Treatments
A meta-analysis of seven RCTs comparing
tamoxifen vs. conservative management,
comprising 898 patients, showed neither
antitumoral effect nor survival benefit of
tamoxifen. Thus, this treatment is
discouraged in advanced HCC.
Systemic chemotherapy has been tested
in nine RCT. The most active agents in
vitro and in vivo are doxorubicin and
cisplatin. Systemic doxorubicin has been
tested in more than 1000 patients within
clinical trials and provides partial
responses in around 10% of cases, without
any evidence of survival advantages .

Chemotherapy
Palliative not Curative.
Regional (Intra-arterial) better that
systemic.
Resistant to many agents.

Summary

Early-stage hepatocellular carcinoma is typically clinically silent, and

HCC is often advanced at first manifestation.
Without treatment, the 5-year survival rate is less than 5%.
Complete surgical resection followed by hepatic transplantation
offers the best long-term survival, but few patients are eligible for
this therapy.
Radiofrequency ablation is the preferred method for managing
unresectable small HCCs that are few in number. More widespread
disease is treated with percutaneous therapies such as
chemoembolization.
Systemic administration of biologic and chemotherapeutic agents is
minimally successful in slowing the growth of HCC and typically is
used to control symptoms in patients with overwhelming disease.
A multidisciplinary approach that includes surgery, systemic
therapy, and radiation therapy and that is based on the cooperation
of radiation oncologists, interventional and diagnostic radiologists,
hepatologists, and pathologists offer the best chance of a cure or at
least a longer and more normal life.

hepatoma